POS0205 SAFETY AND TOLERABILITY OF NINTEDANIB IN PATIENTS WITH AUTOIMMUNE DISEASE-RELATED INTERSTITIAL LUNG DISEASES (ILDs) IN SUBGROUPS BY SEX AND AGE
Authors: A. M. Hoffmann-Vold, E. Volkmann, Y. Allanore, S. Assassi, J. de Vries-Bouwstra, V. Smith, I. Tschoepe, L. Loaiza, M. Kanakapura, O. Distler
Journal: Annals of the Rheumatic Diseases (2022)

Background Nintedanib slows the progression of fibrosing ILDs, with a safety profile characterised predominantly by gastrointestinal events. Objectives Assess the safety and tolerability of nintedanib in patients with autoimmune disease-related ILDs by sex and age. Methods The SENSCIS trial was conducted in patients with ILD associated with systemic sclerosis. The INBUILD trial was conducted in patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis. Patients were randomised to receive nintedanib 150 mg bid or placebo. Dose reductions to 100 mg bid and treatment interruptions were permitted to manage adverse events (AEs). Data from all patients in SENSCIS and patients with autoimmune disease-related ILDs in INBUILD were pooled. In subgroups based on sex and age (&lt;65 and ≥65 years) at baseline, we analysed AEs, irrespective of causality, over 52 weeks. Results Among 746 patients; 70.1% were female; 29.1% were aged ≥65 years. Mean (SD) exposure to nintedanib or placebo was 10.8 (3.2) and 11.1 (2.9) months in females and males, and 11.0 (3.0) and 10.6 (3.5) months in patients aged &lt;65 and ≥65 years, respectively. The AE profile of nintedanib was similar between males and females, but nausea, vomiting, hepatic adverse events and dose reductions were more frequent in females. The AE profile of nintedanib was similar between patients aged &lt;65 and ≥65 years, but nausea, decreased appetite, and weight loss were more frequent in patients aged ≥65 years. AEs leading to treatment discontinuation were more frequent in patients aged ≥65 years in both treatment groups. Serious AEs were more frequent in males and in patients aged ≥65 years in both treatment groups. Conclusion In patients with autoimmune-disease related ILDs, the AE profile of nintedanib in subgroups by sex and age was generally consistent with the known safety profile, but certain types of AE and dose reductions were more frequent in female patients, while serious AEs were more common in male patients. Table 1. Adverse events in patients with autoimmune disease-related ILDs in the SENSCIS and INBUILD trials in subgroups by sex and age at baseline. Female Male Age &lt;65 years Age ≥65 years Nintedanib(n=268) Placebo(n=255) Nintedanib(n=102) Placebo(n=121) Nintedanib(n=267) Placebo(n=262) Nintedanib(n=103) Placebo(n=114) Most frequent adverse events* Diarrhoea 198 (73.9) 77 (30.2) 73 (71.6) 38 (31.4) 197 (73.8) 85 (32.4) 74 (71.8) 30 (26.3) Nausea 92 (34.3) 35 (13.7) 21 (20.6) 14 (11.6) 86 (32.2) 38 (14.5) 27 (26.2) 11 (9.6) Vomiting 73 (27.2) 22 (8.6) 12 (11.8) 14 (11.6) 61 (22.8) 27 (10.3) 24 (23.3) 9 (7.9) Skin ulcer 42 (15.7) 37 (14.5) 12 (11.8) 13 (10.7) 42 (15.7) 45 (17.2) 12 (11.7) 5 (4.4) Nasopharyngitis 34 (12.7) 41 (16.1) 12 (11.8) 21 (17.4) 33 (12.4) 43 (16.4) 13 (12.6) 19 (16.7) Weight decreased 34 (12.7) 8 (3.1) 10 (9.8) 6 (5.0) 29 (10.9) 9 (3.4) 15 (14.6) 5 (4.4) Decreased appetite 29 (10.8) 9 (3.5) 13 (12.7) 4 (3.3) 25 (9.4) 10 (3.8) 17 (16.5) 3 (2.6) Abdominal pain 32 (11.9) 18 (7.1) 8 (7.8) 5 (4.1) 27 (10.1) 19 (7.3) 13 (12.6) 4 (3.5) Upper respiratory tract infection 30 (11.2) 31 (12.2) 9 (8.8) 8 (6.6) 31 (11.6) 33 (12.6) 8 (7.8) 6 (5.3) Cough 23 (8.6) 39 (15.3) 13 (12.7) 19 (15.7) 27 (10.1) 46 (17.6) 9 (8.7) 12 (10.5) Liver-related investigations, signs and symptoms 49 (18.3) 11 (4.3) 13 (12.7) 6 (5.0) 42 (15.7) 12 (4.6) 20 (19.4) 5 (4.4) Adverse event(s) leading to dose reduction 101 (37.7) 9 (3.5) 18 (17.6) 3 (2.5) 81 (30.3) 9 (3.4) 38 (36.9) 3 (2.6) Adverse event(s) leading to treatment discontinuation 44 (16.4) 21 (8.2) 17 (16.7) 13 (10.7) 39 (14.6) 18 (6.9) 22 (21.4) 16 (14.0) Serious adverse event(s) 57 (21.3) 53 (20.8) 40 (39.2) 37 (30.6) 63 (23.6) 54 (20.6) 34 (33.0) 36 (31.6) n (%) of patients with ≥1 such adverse event over 52 weeks. Adverse events were coded based on preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA), except for liver-related investigations, signs and symptoms, which was based on a standardised MedDRA query. *Adverse events reported in &gt;10% of patients with autoimmune disease-related ILDs in the nintedanib or placebo group. Acknowledgements The SENSCIS and INBUILD trials were funded by Boehringer Ingelheim. Oliver Distler was a member of the SENSCIS trial Steering Committee. Disclosure of Interests Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Paid instructor for: Boehringer Ingelheim, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Elizabeth Volkmann Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, Corbus, Forbius, Horizon, Kadmon, Yannick Allanore Consultant of: Abbvie, Astra-Zeneca, Bayer, Boehringer, Mylan, Janssen, Medsenic, Prometheus, Roche, Sanofi, Grant/research support from: Alpine Immunosciences, Medsenic, OSE immunotherapeutics, Shervin Assassi Speakers bureau: On speaker bureau for Integrity Continuing Education, Consultant of: Abbvie, AstraZeneca, Boehringer Ingelheim, CSL Behring, Novartis, Grant/research support from: Boehringer Ingelheim, Janssen, Jeska de Vries-Bouwstra Speakers bureau: Boehringer Ingelheim, Janssen, Consultant of: Abbvie, Boehringer Ingelheim, Grant/research support from: Galapagos NV, Janssen and Roche B.V., Vanessa Smith Speakers bureau: Actelion Pharmaceuticals, Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV, UCB Biopharma Sprl , Consultant of: Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV , Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV, Research Foundation - Flanders (FWO) , Inga Tschoepe Employee of: Inga Tschoepe is an employee of Elderbrook Solutions that is contracted by Boehringer Ingelheim., Lazaro Loaiza Employee of: Lazaro Loaiza is an employee of Boehringer Ingelheim, Madhu Kanakapura Employee of: Madhu Kanakapura is an employee of Boehringer Ingelheim, Oliver Distler Speakers bureau: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: Speaker fee: Bayer, Boehringer Ingelheim, Janssen, Medscape , Consultant of: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: Consultancy fee: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur OD has/had relationships with the following companies in the area of potential treatments for arthritides in the last three calendar years: Consultancy fee: Abbvie , Grant/research support from: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: Research Grants: Boehringer Ingelheim, Kymera, Mitsubishi Tanabe